Daratumumab

GLASGOW, Scotland--(BUSINESS WIRE)--Multiple myeloma, long considered incurable, now has a rigorous definition of cure. The announcement led the International Myeloma Society’s (IMS) 23rd Annual Meeting, attended by over 4,000 people from more than 79 countries. “We are no longer debating whether [myeloma] cure is possible.” — Dr. Nikhil C. Munshi Nikhil C. Munshi, MD, presented the definition developed by IMS and the International Myeloma Working Group. A patient may be considered cured after five years in complete remission without myeloma treatment, counted from when treatment ends. The criteria include at least four negative measurable residual disease (MRD) tests, including one at five years, sensitive enough to detect one myeloma cell in a million. Imaging must show no disease at the start and end. “We are no longer debating whether cure is possible,” said Dr. Munshi, IMS’s immediate past president. “We are defining it rigorously, measuring it precisely, and expanding the number of patients who can achieve it.” Breakthrough data presented at the meeting included: Longer remission after initial treatment: In the Phase 3 PERSEUS trial, 81.1% of patients receiving a daratumumab-containing four-drug regimen were progression-free at six years, versus 56.1% receiving a three-drug regimen. The analysis followed patients for nearly seven years. New options at relapse: In the Phase 3 CERVINO trial, 74% of patients responded to investigational etentamig versus 45.7% receiving available therapies. In EXCALIBER-RRMM, 41.1% receiving iberdomide with daratumumab and dexamethasone achieved MRD-negative complete response versus 20.7% receiving daratumumab, bortezomib and dexamethasone. CAR T generated inside the body: In first-in-human research involving nine patients, seven of eight evaluable patients showed clinical responses after a single infusion designed to generate dual-targeting CAR T cells inside the body. Median follow-up was two months. Other sessions addressed blood-based monitoring, immune protection and the biology of high-risk disease. Bone marrow testing remains the standard for assessing residual disease. IMS26 Abstracts Book: https://www.myelomasociety.org/publications/ On-demand meeting content: myelomasociety.org. About the International Myeloma Society The International Myeloma Society is the only global non-profit focused on myeloma research and clinical care. Representing thousands of experts across more than 75 countries, IMS accelerates cures, fosters collaboration, and transforms patient care. The organization emphasizes funding research (with $18.5 Million Provided) and advancing clinical care access in low-to-middle income countries.

Results presented at IMS 2026 show ZENBEXUS in combination with daratumumab and dexamethasone doubled minimal residual disease-negative complete response rates versus daratumumab, bortezomib and dexamethasone (41.1% vs. 20.7%) Data reinforce the value of the ZENBEXUS-based triplet as an effective, easily administered treatment option for patients with relapsed or refractory multiple myeloma as early as first relapse Results simultaneously published in The Lancet Oncology Bristol Myers Squibb (NYSE: BMY) today announced first time presentation of results from the prespecified analysis of the pivotal Phase 3 EXCALIBER-RRMM trial (NCT04975997) evaluating ZENBEXUS™(iberdomide) in combination with daratumumab and dexamethasone (ZDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma (RRMM). At a median follow-up of 15.7 months in 420 evaluable patients, the study showed a statistically significant and clinically meaningful improvement in minimal residual disease (MRD)-negative complete response (CR) rate, with significantly more patients achieving an MRD-negative CR with ZDd compared to DVd (41.1% vs. 20.7% [95% CI: 11.5%–28.6%]; p<0.0001; odds ratio 2.75 [95% CI: 1.77–4.30]). The dual primary endpoints of the study are MRD-negative CR rate and progression-free survival (PFS). These data are being presented today in a late-breaking oral presentation [Abstract #LBA12] at the 23rd Annual Meeting of the International Myeloma Society (IMS 2026) taking place in Glasgow, Scotland (September 23–26, 2026). These data were also simultaneously published in The Lancet Oncology. Treatment benefit with ZDd was consistent across prespecified subgroups, including patients with prior lenalidomide exposure, and refractoriness to lenalidomide (including in the last prior line of treatment). The overall response rate (ORR) was 88.9% with ZDd compared to 76.1% with DVd, and the rate of complete response or better was also nearly doubled at 45.9% vs. 24.9%, respectively. “Achieving deep, MRD-negative complete responses early in relapse is strongly associated with long-term clinical benefit and overall disease control for patients with multiple myeloma,” said Sagar Lonial, MD, FACP, Professor and Chair of the Department of Hematology and Medical Oncology, Emory University School of Medicine, and Chief Medical Officer, Winship Cancer Institute of Emory University. “These detailed EXCALIBER-RRMM results demonstrate that adding oral iberdomide to this regimen doubled the rate of MRD-negative complete responses or better across subgroups compared to standard DVd, and delivered high rates of overall and complete responses, reinforcing the triplet as a highly effective and manageable regimen that can be easily administered across diverse care settings, including community practices.” The safety pro ZDd was consistent with what is expected of the combination. Grade 3/4 neutropenia occurred in 84.3% of patients treated with ZDd vs. 11.3% treated with DVd, occurring predominantly during the first two cycles. Neutropenia was mostly manageable with G-CSF support and temporary dose interruptions (dose reduction of ZENBEXUS due to neutropenia was 13.2%; discontinuation of ZENBEXUS due to neutropenia was 1.0%). Grade 3/4 infections occurred in 39.2% of patients treated with ZDd vs. 21.6% with DVd, with fatal infections remaining low (2.0% vs. 1.5%). Notably, rates of peripheral sensory neuropathy were markedly lower with ZDd compared with DVd (any grade: 12.3% vs. 42.6%; Grade 3/4: 2.9% vs. 5.4%). “These Phase 3 results reinforce the potential of ZENBEXUS to advance treatment for patients with relapsed or refractory multiple myeloma,” said Cristian Massacesi, executive vice president, chief medical officer and head of development, Bristol Myers Squibb. “As the first therapy in multiple myeloma to demonstrate superiority on an MRD-negative complete response primary endpoint, ZENBEXUS marks an important advance for patients and further validates the potential of targeted protein degradation to expand what is possible in multiple myeloma.” Based on these results from EXCALIBER-RRMM, ZENBEXUS in combination with daratumumab and hyaluronidase-fihj and dexamethasone received accelerated approval from the U.S. Food and Drug Administration for the treatment of adult patients with multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent on August 13th, marking the arrival of a new treatment class. Evaluation of the dual primary endpoint of PFS in the confirmatory analysis cohort (n=800) is ongoing. Bristol Myers Squibb extends its gratitude to the patients, families, and investigators involved in the EXCALIBER-RRMM clinical trial. EXCALIBER-RRMM (NCT04975997) is a Phase 3, multicenter, two-stage, randomized, open-label study evaluating the efficacy and safety of ZENBEXUS (iberdomide) in combination with daratumumab and dexamethasone (ZDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma (RRMM). The study included a dose optimization stage and was designed to assess dual-primary endpoints of minimal residual disease (MRD)-negative complete response (CR) rate and progression-free survival (PFS), with additional secondary endpoints including overall survival (OS), overall response rate (ORR), safety and sustained MRD negativity. Eligible participants included adults with 1 to 2 prior lines of anti-myeloma therapy with progressive disease. A total of 939 patients were randomized. The primary efficacy population for MRD-negative CR included the first 420 patients randomized to the ZENBEXUS (1 mg) + Dd arm (n=207) or the comparator daratumumab, bortezomib, and dexamethasone (DVd) arm (n=213). Treatment in both arms was administered until disease progression or unacceptable toxicity. Targeted protein degradation (TPD) is a differentiated research platform at Bristol Myers Squibb built on more than two decades of scientific expertise, providing new avenues to degrade therapeutically relevant proteins that were previously considered difficult to address. BMS is the only company that has successfully developed and commercialized protein degrader agents for the treatment of multiple myeloma. These agents, known as immunomodulatory drugs (IMiDs), helped establish the current standard of care in the treatment of this disease, which remains without a cure. BMS is building on this foundation with several investigational protein degraders in clinical trials, leveraging three different modalities including cereblon E3 ligase modulators (CELMoDs), ligand-directed degraders (LDDs), and degrader antibody conjugates (DACs). This three-pronged approach enables matching the right therapeutic modality to a molecular mechanism of action to modulate targets most effectively and ultimately provides more opportunities for potential breakthroughs that may offer meaningful new options for patients across a broad range of diseases, in and beyond hematology and oncology. ZENBEXUS™ is also being evaluated in the EXCALIBER Maintenance study. At Bristol Myers Squibb, our mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. 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